DESCRIPTION (Taken from application abstract): This project is directed at understanding the structure and function of synapses in the developing and mature brain, by quantitative and three-dimensional analysis of the structure, connectivity, and plasticity of presynaptic, postsynaptic, and glial elements. Such knowledge subserves understanding of the role of synaptic abnormalities in mental retardation. The informatics objective is to improve the methods of quantitative analysis and availability of anatomical data at the ultrastructural level by: 1. Developing an internet-accessible repository of synaptic and perisynaptic anatomy that will serve as a community resource for connecting the molecular and neuron levels of analyses. 2. Developing software for the public-domain that is internet accessible and third-party extensible to support and facilitate input and output of the database. 3. Improving the speed and accuracy of acquisition, alignment, calibration, segmentation, and 3D reconstruction of serial electron microscope sections from brain. 4. Developing software tools for quantitative comparison of different pre- and postsynaptic geometries and patterns of connectivity. The brain research objective is to test how synaptic structures can regulate synaptic function during development and plasticity by: 1. Investigating how synaptic and perisynaptic anatomy, change during development, during maintenance of slices in vitro, and during long-term potentiation (LTP) and long-term depression (LTD). 2. Examining how synaptic and perisynaptic anatomy differs during different levels of brain activity (hibernation, arousal, and wakeful activity). 3. Investigating the quantitative changes in spine and dendritic calcium due to activation of receptors coupled to the phosphoinositide second messenger system and determining the role this calcium signal plays in different types of synaptic plasticity (LTP, LTD, hibernation) using anatomical models from the database.